Molecular mechanisms of apoptosis induced by 3'-ethynylcytidine.

Yusuke Wataya, Tomoharu Naito, Akira Sato, Akiko Hiramoto, Yukio Kitade, Takuma Sasaki, Akira Matsuda, Masakazu Fukushima, Hye-Sook Kim

Research output: Contribution to journalArticle

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Abstract

1-(3-C-Ethynyl-beta-D-ribo-pentofuranosyl)cytosine (3'-Ethynylcytidine; ECyd), a ribonucleoside analog, has a potent cytotoxic activity against cancer cells. We have investigated the cancer-cell death induced by ECyd, focusing on its molecular mechanisms. In ECyd-treated cells, RNase L is activated and involved in c-jun NH(2)-terminal kinase (JNK) phosphorylation, followed by induction of mitochondria-dependent apoptosis. The mechanism of JNK phophorylation by RNase L was unknown. To investigate the mechanism, we performed the identification of RNase L-binding partners by proteomic approach using co-immunoprecipitation and mass spectrometry. We found that RNase L was associated with a protein (we named it Protein-190). At the same time, we observed that Protein-190 was amply phosphorylated. Furthermore, the participation of Protein-190 in the ECyd-induced apoptosis was supported by a knockdown experiment using small interfering RNA (siRNA). Thus, the number of ECyd-induced apoptotic cells was drastically decreased when Protein-190 was knocked-down. These results indicated Protein-190 as a regulator in apoptosis, and provide the possibility for a new clinical target in cancer chemotherapy.

Original languageEnglish
Pages (from-to)291-292
Number of pages2
JournalNucleic acids symposium series (2004)
Issue number53
Publication statusPublished - 2009

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Apoptosis
Proteins
MAP Kinase Kinase 4
Ribonucleosides
Neoplasms
Immunoprecipitation
Proteomics
Small Interfering RNA
1-(3-C-ethynylribopentofuranosyl)cytosine
Mass Spectrometry
Mitochondria
Cell Death
Phosphorylation
Drug Therapy
2-5A-dependent ribonuclease

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wataya, Y., Naito, T., Sato, A., Hiramoto, A., Kitade, Y., Sasaki, T., ... Kim, H-S. (2009). Molecular mechanisms of apoptosis induced by 3'-ethynylcytidine. Nucleic acids symposium series (2004), (53), 291-292.

Molecular mechanisms of apoptosis induced by 3'-ethynylcytidine. / Wataya, Yusuke; Naito, Tomoharu; Sato, Akira; Hiramoto, Akiko; Kitade, Yukio; Sasaki, Takuma; Matsuda, Akira; Fukushima, Masakazu; Kim, Hye-Sook.

In: Nucleic acids symposium series (2004), No. 53, 2009, p. 291-292.

Research output: Contribution to journalArticle

Wataya, Y, Naito, T, Sato, A, Hiramoto, A, Kitade, Y, Sasaki, T, Matsuda, A, Fukushima, M & Kim, H-S 2009, 'Molecular mechanisms of apoptosis induced by 3'-ethynylcytidine.', Nucleic acids symposium series (2004), no. 53, pp. 291-292.
Wataya Y, Naito T, Sato A, Hiramoto A, Kitade Y, Sasaki T et al. Molecular mechanisms of apoptosis induced by 3'-ethynylcytidine. Nucleic acids symposium series (2004). 2009;(53):291-292.
Wataya, Yusuke ; Naito, Tomoharu ; Sato, Akira ; Hiramoto, Akiko ; Kitade, Yukio ; Sasaki, Takuma ; Matsuda, Akira ; Fukushima, Masakazu ; Kim, Hye-Sook. / Molecular mechanisms of apoptosis induced by 3'-ethynylcytidine. In: Nucleic acids symposium series (2004). 2009 ; No. 53. pp. 291-292.
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